Dietary blueberry ameliorates vascular complications in diabetic mice possibly through NOX4 and modulates composition and functional diversity of gut microbes

Authors: PETERSEN, CHRISSA - University Of Colorado; DHARAT, DIVYA - University Of Colorado; WANKHADE, UMESH - Arkansas Children'S Nutrition Research Center (ACNC); KIM, JI-SEOK - University Of Colorado; CUTLER, BRETT - University Of Colorado; DENETSO, CHRISTOPHER - University Of Colorado; GHOLAMI, SAMIRA - University Of Colorado; NELSON, SAMANTHA - University Of Colorado; BIGLEY, JESSICA - University Of Colorado; JOHNSON, ASPEN - University Of Colorado; CHINTAPALLIV, SREE - Arkansas Children'S Nutrition Research Center (ACNC); PICCOLO, BRIAN - Arkansas Children'S Nutrition Research Center (ACNC); SATHEESH BABU, ADHINI - University Of Colorado; PAZ, HENRY - Arkansas Children'S Nutrition Research Center (ACNC); SHANKAR, KARTIK - University Arkansas For Medical Sciences (UAMS); SYMONS, DAVID - University Of Colorado; ANANDH BABU, PON VELAY - University Of Colorado

Submitted to: Molecular Nutrition and Food Research
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 1/27/2022
Publication Date: 2/4/2022
Citation: Petersen, C., Dharat, D., Wankhade, U.D., Kim, J., Cutler, B.R., Denetso, C., Gholami, S., Nelson, S., Bigley, J., Johnson, A., Chintapalliv, S., Piccolo, B., Satheesh Babu, A.K., Paz, H.A., Shankar, K., Symons, D., Anandh Babu, P. 2022. Dietary blueberry ameliorates vascular complications in diabetic mice possibly through NOX4 and modulates composition and functional diversity of gut microbes. Molecular Nutrition and Food Research. https://doi.org/10.1002/mnfr.202100784.
DOI: https://doi.org/10.1002/mnfr.202100784

Interpretive Summary: Cardiovascular complications are one of the co-morbidities of obesity. Physiological beneficial effects of blueberry supplementation have been demonstrated in the literature. In the current study, authors fed diabetic mice with freeze dried blueberry powder. Blueberry supplementation reduced the expression of pro-inflammatory pathways in the blood vessel in diabetic mice fed with blueberry. Further, blueberry supplementation increased commensal microbes and improves the functional potential of gut microbes in diabetic mice. In summary, dietary blueberry suppresses vascular inflammation, and supports the growth of commensal microbes in diabetic mice.

Technical Abstract: Scope: In diabetes, endothelial inflammation and dysfunction play a pivotal role in the development of vascular disease. This study investigates the effect of dietary blueberries on vascular complications and gut microbiome in diabetic mice. Methods and Results: Seven-week-old diabetic db/db mice consume a standard diet (db/db) or a diet supplemented with 3.8% freeze-dried blueberry (db/db+BB) for 10 weeks. Control db/+ mice are fed a standard diet (db/+). Vascular inflammation is assessed by measuring monocyte binding to vasculature and inflammatory markers. Isometric tension procedures are used to assess mesenteric artery function. db/db mice exhibit enhanced vascular inflammation and reduced endothelial-dependent vasorelaxation as compared to db/+ mice, but these are improved in db/db+BB mice. Blueberry supplementation reduces the expression of NOX4 and I''K'' in the aortic vessel and vascular endothelial cells (ECs) isolated from db/db+BB compared to db/db mice. The blueberry metabolites serum reduces glucose and palmitate induced endothelial inflammation in mouse aortic ECs. Further, blueberry supplementation increases commensal microbes and modulates the functional potential of gut microbes in diabetic mice. Conclusion: Dietary blueberry suppresses vascular inflammation, attenuates arterial endothelial dysfunction, and supports the growth of commensal microbes in diabetic mice. The endothelial-specific vascular benefits of blueberries are mediated through NOX4 signaling.